Phorboxazole A: Comparative Synthetic Approaches, Bioactivity, and Future Green Chemistry Strategies

Phorboxazole A is a tropical marine macrolide isolated from the sponge Phorbas sp. and has emerged as one of the most potent cytostatic agents found in nature, with nanomolar activity against diverse cancer cell lines and antifungal properties against pathogens like Candida albicans. The structural complexity of Phorboxazole A, characterized by a 46-carbon skeleton, 28 stereocenters, two oxazole rings, and a macrocyclic core, has spurred innovative synthetic campaigns since its isolation 30 years ago. This review article highlights the approaches in total synthesis strategies for phorboxazole A, emphasizing the Petasis-Ferrier union/rearrangement, tri-component coupling, convergent assembly, stereoselective cyclization, and comparative retrosynthetic analysis, followed by discussions regarding its biological activity, and the feasibility of utilizing green chemistry principles in mitigating the hazardous effects on human health and the environment.